Capricor Therapeutics Inc (CAPR) 2024 Q4 法說會逐字稿

Good afternoon, ladies and gentlemen, and welcome to the Capricor Therapeutics' second-quarter (sic - "fourth-quarter") 2024 earnings call. (Operator Instructions) This call is being recorded on Wednesday, March 19, 2025.

女士們、先生們，下午好，歡迎參加 Capricor Therapeutics 2024 年第二季度（原文如此 - “第四季度”）收益電話會議。（操作員指示）此通話於 2025 年 3 月 19 日星期三錄製。

I would now like to turn the conference over to our CFO, AJ Bergmann, for the forward-looking statement. Please go ahead.

現在，我想將會議交給我們的財務長 AJ Bergmann 來發表前瞻性聲明。請繼續。

Thank you, and good afternoon, everyone. Before we start, I would like to state that we will be making certain forward-looking statements during today's presentation. These statements may include statements regarding, among other things, the efficacy, safety, and intended utilization of our product candidates, our future R&D plans, including our anticipated conduct and timing of preclinical and clinical studies, our enrollment of patients in our clinical studies, our plans to present or report additional data, our plans regarding regulatory filings, potential regulatory developments involving our product candidates, revenue and reimbursement estimates, projected terms of definitive agreements, manufacturing capabilities, potential milestone payments, our financial position, and our possible uses of existing cash and investment resources.

謝謝大家，下午好。在我們開始之前，我想聲明一下，我們將在今天的演講中做出一些前瞻性的陳述。這些聲明可能包括關於我們候選產品的功效、安全性和預期用途、我們未來的研發計劃（包括我們預期進行的臨床前和臨床研究及其時間安排）、我們臨床研究中的患者招募情況、我們提交或報告額外數據的計劃、我們關於監管備案的計劃、涉及我們候選產品的潛在監管發展、收入和報銷估計、最終的財務狀況、我們預期

These forward-looking statements are based on current information, assumptions, and expectations that are subject to change and involve a number of risks and uncertainties that may cause actual results to differ materially from those contained in the forward-looking statements. These and other risks are described in our periodic filings made with the SEC, including our quarterly and annual reports.

這些前瞻性陳述是基於當前資訊、假設和預期，這些資訊、假設和預期可能會發生變化，並涉及許多風險和不確定性，可能導致實際結果與前瞻性陳述中的結果有重大差異。這些風險和其他風險在我們向美國證券交易委員會提交的定期文件中有所描述，包括我們的季度報告和年度報告。

You are cautioned not to place undue reliance on these forward-looking statements, and we disclaim any obligation to update such statements.

請注意不要過度依賴這些前瞻性陳述，我們不承擔更新此類陳述的任何義務。

With that, I'll turn the call over to Linda Marbán, CEO.

說完這些，我將把電話轉給執行長 Linda Marbán。

Thanks, AJ. Good afternoon, everyone, and thank you for joining today's conference call.

謝謝，AJ。大家下午好，感謝大家參加今天的電話會議。

The mission of Capricor has always been to discover and develop transformative drug products for patients in need and translating these biological medicines into commercial products. As many of you know, Capricor was founded over 20 years ago, originally in the laboratories at Johns Hopkins University, where we isolated, characterized, and harnessed a unique cell type derived from heart tissue.

Capricor 的使命一直是為有需要的患者發現和開發轉化藥物產品，並將這些生物藥物轉化為商業產品。眾所周知，Capricor 成立於 20 多年前，最初位於約翰霍普金斯大學的實驗室，我們在那裡分離、表徵和利用了來自心臟組織的獨特細胞類型。

Even at that time of discovery, the cardiosphere-derived cells, which are now known as deramiocel, were conceptualized to potentially be a powerful cellular therapeutic which one day could treat diseases of the heart, for which there are many.

甚至在那個發現時期，心臟球衍生細胞（現在被稱為 deramiocel）就被認為可能是一種強大的細胞療法，有朝一日可以治療多種心臟疾病。

Now let me remind you that deramiocel has a defined mechanism of action which is primarily immunomodulatory and anti-fibrotic driven by the release of exosomes after the cells are infused. Our identity and potency assays, which are supported by the FDA, are based on those properties of bioactivity.

現在讓我提醒您，deramiocel 具有明確的作用機制，其主要作用是免疫調節和抗纖維化，由細胞注入後釋放的外泌體驅動。我們的身份和效力分析是基於生物活性的特性進行的，並得到了 FDA 的支持。

Deramiocel is not a stem cell, let me remind you. Its active ingredient is a rarefied population of cardiac cells that Capricor isolates and expands using proprietary methods. Cells are infused in a simple, one-time per quarter intravenous infusion at a dose of 150 million cells. With over 700 infusions of the product over many years, deramiocel has been shown to be a safe and effective means for attenuating disease progression.

讓我提醒你一下，Deramiocel 不是乾細胞。其活性成分是 Capricor 使用專有方法分離和擴增的稀有心臟細胞群。細胞輸注方式簡單，每季進行一次靜脈輸注，劑量為 1.5 億個細胞。多年來，該產品已輸注超過 700 次，證明 deramiocel 是一種安全有效的減緩病情進展的方法。

As many of we have been working for over eight years developing deramiocel as a treatment for those impacted by Duchenne muscular dystrophy. And it is with great pride and joy that I can say we find ourselves potentially nearing approval.

我們中的許多人已經工作了八年多，致力於開發 deramiocel，以治療杜氏肌肉營養不良症患者。我可以非常自豪和高興地說，我們可能已經接近獲得批准。

Today, I will walk you through the latest regulatory, DMC, and commercial updates as Capricor begins to transition from a translational medicines company to a potentially commercial stage company. We will continue to stay committed to our mission, developing transformational treatments for patients in need and driving value for our shareholders.

今天，我將向您介紹最新的監管、DMC 和商業更新，因為 Capricor 開始從一家轉化醫學公司轉型為潛在的商業階段公司。我們將繼續致力於我們的使命，為有需要的患者開發變革性治療方法並為我們的股東創造價值。

Now turning first to our biologic license application, or BLA, filing for DMD cardiomyopathy, which we announced in early March was accepted by FDA for priority review.

現在先談談我們的生物製品許可申請（BLA），即 DMD 心肌病變的申請，我們在 3 月初宣布該申請已被 FDA 接受優先審查。

The application is seeking full, not accelerated, approval of deramiocel to treat DMD cardiomyopathy, an aspect of the disease that not only afflicts essentially all DMD patients but also as the leading cause of mortality associated with DMD.

該申請尋求對 deramiocel 治療 DMD 心肌病變的完全批准（而非加速批准），DMD 心肌病變不僅折磨著基本上所有的 DMD 患者，而且是 DMD 相關死亡的主要原因。

As we look ahead to our PDUFA date set for August 30, 2025, we are working with the FDA as they are actively reviewing our application. At this time, the FDA has not indicated to us whether an ADCOM will be necessary, but we are preparing for one should that be needed, and I am pleased to inform you that we have officially scheduled our PLI, or pre-licensing inspection of our manufacturing facility, which is set for the second quarter of this year.

展望 2025 年 8 月 30 日的 PDUFA 日期，我們正在與 FDA 合作，他們正在積極審查我們的申請。目前，FDA 尚未向我們表明是否需要 ADCOM，但我們正在為必要時的 ADCOM 做準備，我很高興地通知您，我們已正式安排了 PLI 或製造工廠的許可前檢查，該檢查將於今年第二季度進行。

Our BLA is supported with data from two trials: our Phase 2 HOPE-2, placebo-controlled trial, and our HOPE-2, open label extension trial compared to patient level, natural history data from the DMD Cardiac Consortium led by Dr. Jonathan Soslow at Vanderbilt University.

我們的 BLA 得到了兩項試驗數據的支持：我們的第 2 階段 HOPE-2 安慰劑對照試驗，以及我們的 HOPE-2 開放標籤擴展試驗，與患者層級、范德比爾特大學 Jonathan Soslow 博士領導的 DMD 心臟聯盟的自然歷史數據進行比較。

Many factors have given us confidence in our BLA submission pathway. First and foremost, it has a strong safety profile and has been administered to over 250 human subjects across several clinical trials over multiple years. Equally as important is that the data continues to show clinical and statistically significant efficacy in the treatment of DMD cardiomyopathy. This data is foundational to our BLA filing.

許多因素使我們對 BLA 提交途徑充滿信心。首先，它具有很強的安全性，並且已經在多年的多次臨床試驗中對超過 250 名人類受試者進行了試驗。同樣重要的是，數據繼續顯示在治療 DMD 心肌病變方面具有臨床和統計學上顯著的療效。這些數據是我們 BLA 備案的基礎。

I would also like to point out that it has become well known that the cardiac and skeletal aspects of the disease do not decline at the same rate. So therefore, because we see an impact on both cardiac and skeletal muscle function, we are confident that we are seeing a treatment effect of deramiocel across multiple domains, further strengthening the opportunity to treat DMD with deramiocel.

我還想指出，眾所周知，這種疾病的心臟和骨骼方面的衰退速度並不相同。因此，由於我們看到了對心臟和骨骼肌功能的影響，我們相信我們看到了 deramiocel 在多個領域的治療效果，進一步加強了使用 deramiocel 治療 DMD 的機會​​。

Furthermore, as exhibited this week at the Muscular Dystrophy Association conference, we see a year-over-year improvement in function, suggesting that long-term use of deramiocel is warranted for the treatment of DMD.

此外，正如本週肌肉萎縮症協會會議上所展示的那樣，我們看到功能逐年改善，這表明長期使用 deramiocel 治療 DMD 是合理的。

We also have continued to work in close collaboration with the FDA. We have been the beneficiaries of CBER's approach to drug development and believe that with the combination of statistically and clinically significant data that addresses an unmet medical need, we are well poised to gain approval of deramiocel for DMD cardiomyopathy.

我們也繼續與 FDA 密切合作。我們一直是 CBER 藥物開發方法的受益者，並相信透過結合統計和臨床意義的數據來解決未滿足的醫療需求，我們已準備好獲得 deramiocel 用於治療 DMD 心肌病變的批准。

In addition, our RMAT designation allows us to work directly with FDA as we realize the true goal here is to bring the first treatment to market for DMD cardiomyopathy for which there are no approved therapies.

此外，我們的 RMAT 資格使我們能夠直接與 FDA 合作，因為我們意識到我們的真正目標是將第一種治療 DMD 心肌病變的療法推向市場，而目前還沒有針對該疾病的療法獲得批准。

Lastly, throughout 2024, we met with the FDA multiple times outlining our BLA filing strategy, of which we have discussed previously, and I want to reiterate that they have not requested the HOPE-3 data, and currently, we do not believe it will be necessary to support our application.

最後，在整個 2024 年，我們多次與 FDA 會面，概述了我們的 BLA 申請策略，我們之前已經討論過該策略，我想重申，他們沒有要求提供 HOPE-3 數據，目前，我們認為沒有必要支持我們的申請。

As you may recall, the HOPE-3 clinical trial has a primary efficacy endpoint of the performance of the upper limb version 2.0, which is an indicator of skeletal muscle function. We plan to use this data in the future for potential label expansion. To that end, we are currently evaluating the plans for HOPE-3 and will provide more updates as they become available.

大家可能還記得，HOPE-3臨床試驗的主要療效終點是上肢2.0版的表現，這是骨骼肌功能的指標。我們計劃在未來使用這些數據來擴展潛在的標籤。為此，我們目前正在評估 HOPE-3 的計劃，並將在獲得更多更新後提供。

Now turning our attention to commercial planning. We are actively working with our commercial partner, NS Pharma, on launch readiness for the United States. Key areas of overlapping focus are market access and reimbursement.

現在我們將注意力轉向商業規劃。我們正積極與我們的商業夥伴 NS Pharma 合作，為在美國推出產品做好準備。重點重疊的領域是市場准入和報銷。

Their team in the United States is comprised of approximately 125 people with market access, reimbursement, medical affairs, and sales teams actively preparing for the launch of deramiocel in the United States.

他們在美國團隊約有 125 人，擁有市場准入、報銷、醫療事務和銷售團隊，積極為在美國推出 deramiocel 做準備。

We recently completed surveys with the top 5 payers in the US with the response coming in very favorably from a reimbursement standpoint for deramiocel. Since there are currently no approved therapies for DMD cardiomyopathy, and data suggests that standard cardiac medications do not have a significant impact on disease progression in most cases, we see deramiocel as a transformational treatment option for these boys and young men.

我們最近對美國前五大付款人進行了調查，從 deramiocel 的報銷角度來看，他們的反應非常積極。由於目前尚無批准的 DMD 心肌病變療法，且數據顯示標準心臟藥物在大多數情況下對疾病進展沒有顯著影響，我們將 deramiocel 視為這些男孩和年輕男性的轉型治療選擇。

We expect reimbursement would be consistent with other recently approved DMD therapies such as exon skippers. If approved, we are anticipating that approximately 50% to 60% of the overall DMD population in the United States, or around 7,500 boys and young men with DMD, would be eligible for treatment with deramiocel.

我們預計報銷將與其他最近批准的 DMD 療法（如外顯子跳躍療法）一致。如果獲得批准，我們預計美國大約 50% 至 60% 的 DMD 患者，或大約 7,500 名患有 DMD 的男孩和年輕男性，將有資格接受 deramiocel 治療。

If approved, we are anticipating entering the market with approximately 100 patients transferring from our open label extension trial to commercial products. This would drive revenue to the bottom line. To remind you, in the US, we are entitled to between 30% to 50% of revenue share based on sales of the product inclusive of cost of goods sold.

如果獲得批准，我們預計將有大約 100 名患者從我們的開放標籤擴展試驗轉向商業產品。這將推動收入成長。提醒您，在美國，我們有權根據產品銷售額（包括銷售成本）獲得 30% 至 50% 的收入分成。

I'd like to shift our attention to CMC, or chemistry manufacturing and control. Our current GMP-compliant facility located in San Diego is fully operational and staffed, producing doses of deramiocel. We built and carefully designed this facility to meet early market demand. The fully operational capacity in this facility can support approximately 250 to 500 patients per year, and we believe will be sufficient to support the anticipated first year of launch.

我想將我們的注意力轉移到 CMC，即化學製造和控制。我們目前位於聖地牙哥的符合 GMP 標準的工廠已全面投入運作並配備人員，生產 deramiocel 劑量。我們建造並精心設計了這個設施以滿足早期市場的需求。該設施的全面運作能力每年可支援約 250 至 500 名患者，我們相信足以支持預計的第一年啟動。

As we expect a strong launch and rapid adoption of deramiocel for DMD cardiomyopathy if approved, I am pleased to announce that we have expanded our current San Diego facility where we have leased an additional 25,000 square feet for which we are going to build additional clean rooms taking our manufacturing capacity to approximately 2,000 to 3,000 patients per year, once completed and fully operational.

一旦獲得批准，我們預計用於治療 DMD 心肌病的 deramiocel 將得到大力推廣和快速普及，我很高興地宣布，我們已經擴建了我們目前的聖地亞哥工廠，我們在該工廠又租賃了 25,000 平方英尺的空間，我們將建造更多的潔淨室，一旦竣工並全面投入運營，我們的生產能力將達到每年約 2,000 名患者。

We have assembled a world class team who is extremely sophisticated in this area, and I have high confidence we will have this new expanded facility online by mid-2026, allowing us to bolster supply of the product for the next several years to meet demand. As we continue to expand our capabilities, we are already looking into product development endeavors to allow us to increase our yield further.

我們已經組建了一支在該領域極其精通的世界級團隊，我非常有信心，我們將在 2026 年中期將這座新的擴建設施投入使用，這使我們能夠在未來幾年加強產品供應，以滿足需求。隨著我們不斷擴大能力，我們已經開始研究產品開發工作，以進一步提高產量。

On the corporate and commercial fronts, we are able to look at our balance sheets. Our cash balance of approximately $150 million is being deployed across the organization with our current runway into 2027 with no additional infusions of cash. If we receive FDA approval, we will be slated to receive an additional $80 million milestone payment from Nippon Shinyaku.

在公司和商業方面，我們可以查看我們的資產負債表。我們的現金餘額約為 1.5 億美元，正在整個組織內部署，目前預計到 2027 年將不再注入現金。如果我們獲得 FDA 批准，我們將從日本新藥公司獲得額外的 8000 萬美元里程碑付款。

And in addition, we would receive a priority review voucher which we have the full rights to sell or transfer. These non-diluted cash infusions could total well over $200 million, which would hit our balance sheet in 2025 alongside our existing cash and potential product revenue. This puts us in a strong position to deliver for our shareholders on multiple fronts.

此外，我們還將獲得優先審查券，我們擁有出售或轉讓該券的全部權利。這些未稀釋現金注入總額可能遠超過 2 億美元，並將與我們現有的現金和潛在產品收入一起在 2025 年進入我們的資產負債表。這使我們處於有利地位，可以在多個方面為股東帶來利益。

Our strong cash position will continue to allow us to strengthen our commercial organization, which includes enhancing our team with commercial and medical expertise in order to fuel future product development opportunities for deramiocel and enable us to build Capricorn into a world-class, revenue-generating, cash flow positive company with a commercial product on the market and a robust pipeline of expansion opportunities leveraging cell and exosome-based therapeutics.

我們強大的現金狀況將繼續使我們能夠加強我們的商業組織，包括透過商業和醫學專業知識增強我們的團隊，以推動 deramiocel 未來的產品開發機會，並使我們能夠將 Capricorn 打造成為一家世界級的、可產生收入的、現金流為正的公司，在市場上擁有商業產品，並擁有利用細胞和外泌體療法的強大機會。

Last, for a brief update on our European partnering efforts. Last year we entered into a term sheet with Nippon Shinyaku for the marketing, sales, and distribution of deramiocel in the European region, subject to finalization of a definitive agreement.

最後，我們簡單介紹一下我們與歐洲的合作情況。去年，我們與日本新藥株式會社簽署了一份條款清單，負責在歐洲地區行銷、銷售和分銷 deramiocel，但最終需要達成最終協議。

Our commitment to Nippon Shinyaku in the USA and Japan as our commercial partner is strong, but we have not yet come to final terms on the definitive agreement which is still being negotiated. In the meantime, we have achieved important regulatory designations in Europe and are on track for meeting with the EMA in the second quarter of 2025. We will provide additional color as our strategy for Europe continues to unfold.

我們堅定地致力於將日本新藥作為我們在美國和日本的商業夥伴，但我們尚未就仍在談判中的最終協議達成最終協議。同時，我們已在歐洲獲得重要的監管資格，並預計在 2025 年第二季與 EMA 會面。隨著我們的歐洲戰略不斷展開，我們將提供更多內容。

Now I'd like to switch gears and give an update on our exosomes pipeline program. We continue to develop our StealthX exosome platform technology as part of a next generation drug delivery platform. Our goal is to build the exosomes into a standardized drug delivery platform that has enhanced capabilities when compared to a lipid nanoparticle, including targeting and delivering contents across the cell membrane.

現在我想換個話題，介紹一下我們的外泌體管道計畫的最新進展。我們將繼續開發 StealthX 外泌體平台技術，作為下一代藥物傳輸平台的一部分。我們的目標是將外泌體建構成一個標準化的藥物傳遞平台，與脂質奈米顆粒相比，該平台具有更強大的功能，包括靶向和跨細胞膜傳遞內容物。

While most of our focus has been on the commercialization of deramiocel, we have had a small team working on building the exosomes in the background. They have successfully designed a manufacturing method that is cost effective and can be expanded to make large amounts necessary for therapeutic delivery. We have presented this proof of concept data at many scientific meetings and published these findings in peer review journals.

雖然我們大部分的精力都集中在 deramiocel 的商業化上，但我們也有一個小團隊在幕後致力於建立外泌體。他們成功設計出一種經濟高效的製造方法，可以擴大生產治療輸送所需的大量產品。我們在許多科學會議上展示了這個概念驗證數據，並在同行評審期刊上發表了這些研究結果。

Our approach is to concurrently demonstrate the utility of the exosomes by developing a vaccine platform that is unique, using native proteins loaded in or coded on an exosome that could be made rapidly within the 100-day constraints developed by the US government, but also able to generate a robust and long lasting immune response. That program is part of the US government's Project NextGen, which aims to test vaccine candidates for COVID-19 prevention in addition to prepare for future pandemics.

我們的方法是透過開發一個獨特的疫苗平台來同時展示外泌體的實用性，使用裝載在外泌體中或在其上編碼的天然蛋白質，這種蛋白質可以在美國政府制定的 100 天限制內快速製造，而且還能夠產生強大而持久的免疫反應。該計劃是美國政府「下一代計劃」的一部分，該計劃旨在測試預防新冠肺炎的候選疫苗，並為未來的大流行做好準備。

Currently, our StealthX vaccine candidate is in the manufacturing phase. The NIAD, which is the National Institute of Allergy and Infectious Disease, will then conduct and fully fund a Phase 1 clinical trial. Currently, manufacturing is underway for our StealthX vaccine, and the NIAD is planning for regulatory approval in the second quarter of 2025 with the clinical study initiated soon thereafter. We will provide further updates on this program as they become available.

目前，我們的 StealthX 候選疫苗正處於生產階段。美國國家過敏和傳染病研究所 (NIAD) 將進行第一階段臨床試驗並全額資助。目前，我們的 StealthX 疫苗正在生產中，NIAD 計劃在 2025 年第二季獲得監管部門批准，並將很快啟動臨床研究。我們將在該計劃發布後提供進一步的更新。

Now that deramiocel is on a defined path towards potential commercialization, we are further evaluating the path forward for a therapeutic exosome pathway and also evaluating other opportunities to expand our future pipeline.

現在，deramiocel 已經走上了實現潛在商業化的明確道路，我們正在進一步評估治療性外泌體途徑的未來發展方向，並評估擴展未來產品線的其他機會。

In conclusion, 2024 was a transformational new year for Capricor, and 2025 is the year in which we will hopefully transition into our next stages of development. I am proud of our progress and grateful to the patients, their families, our investors for their continued support. Capricor's goal is to continue to meet its milestones as we continue to focus on our efforts on bringing deramiocel towards potential commercialization and are investing judiciously across the organization to prepare for that endeavor.

總而言之，2024 年對 Capricor 來說是一個轉型的新年，而 2025 年則是我們希望進入下一發展階段的一年。我為我們的進步感到自豪，並感謝患者、他們的家人以及我們的投資者的持續支持。Capricor 的目標是繼續實現其里程碑，因為我們將繼續致力於將 deramiocel 推向潛在的商業化，並在整個組織內進行明智的投資，為這項努力做好準備。

I will now turn the call over to AJ to run through our financials. AJ.

現在我將把電話轉給 AJ 來介紹我們的財務狀況。AJ。

Thanks, Linda. This afternoon's press release provided a summary of our fourth-quarter and full-year 2024 financials on a GAAP basis. You may also refer to our annual report on Form 10-K, which we expect to become available in the next several days and will be accessible on the SEC website as well as the Financial section of the company website.

謝謝，琳達。今天下午的新聞稿根據 GAAP 提供了我們 2024 年第四季和全年財務狀況的摘要。您也可以參考我們的 10-K 表格年度報告，預計該報告將在未來幾天內發布，並可在美國證券交易委員會 (SEC) 網站以及公司網站的財務部分查閱。

Let me start with our cash position. As of December 31, 2024, our cash, cash equivalents and marketable securities totaled approximately $151.5 million. Subsequent to December 31, 2024, we received a $10 million milestone payment from Nippon Shinyaku pursuant to the terms of our US distribution agreement. So on a pro forma basis, our cash, cash equivalents, and marketable securities would total approximately $161.5 million.

讓我先從我們的現金狀況開始。截至 2024 年 12 月 31 日，我們的現金、現金等價物及有價證券總額約為 1.515 億美元。2024 年 12 月 31 日之後，根據我們美國分銷協議的條款，我們從 Nippon Shinyaku 收到了 1000 萬美元的里程碑付款。因此，以備考基礎，我們的現金、現金等價物和有價證券總額約為 1.615 億美元。

Turning now to the financials. Revenues for the fourth quarter of '24 were approximately $11.1 million compared to approximately $12.1 million for the fourth quarter of 2023. The source of revenue is the ratable recognition of the $40 million we have received from our US distribution agreement with Nippon Shinyaku and the $10 million milestone payment we triggered in December 2024 after we submitted our BLA to the FDA.

現在來談談財務問題。2024 年第四季的營收約為 1,110 萬美元，而 2023 年第四季的營收約為 1,210 萬美元。收入來源是我們與日本新藥株式會社簽訂的美國分銷協議中獲得的 4000 萬美元的按比例確認，以及我們向 FDA 提交 BLA 後於 2024 年 12 月觸發的 1000 萬美元里程碑付款。

Moving to operating expenses for the fourth quarter of '24, excluding stock-based compensation, our research and development expense was approximately $13.6 million compared to approximately $9.4 million in Q4 2023. And again, excluding stock-based compensation, our G&A expense was approximately $3 million in Q4 2024 and approximately $2.1 million in Q4 2023.

轉到 24 年第四季的營運費用（不含股票薪資），我們的研發費用約為 1,360 萬美元，而 2023 年第四季約為 940 萬美元。再次，不包括股票薪酬，我們的 G&A 費用在 2024 年第四季約為 300 萬美元，2023 年第四季約為 210 萬美元。

Net loss for the fourth quarter of 2024 was approximately $7.1 million compared to a net loss of approximately $800,000 for the fourth quarter of 2023. The net loss for the year ended December 31, 2024, was approximately $40.5 million compared to a net loss of approximately $22.3 million for the year ended December 31, 2023.

2024 年第四季淨虧損約 710 萬美元，而 2023 年第四季淨虧損約 80 萬美元。截至 2024 年 12 月 31 日止年度的淨虧損約為 4,050 萬美元，而截至 2023 年 12 月 31 日止年度的淨虧損約為 2,230 萬美元。

We will now open the line up for questions. Operator?

我們現在開始回答問題。操作員？

(Operator Instructions) Ted Tenthoff, Piper Sandler.

（操作員指示）Ted Tenthoff，Piper Sandler。

Great. Thank you very much and congratulations on all of the progress. It's going to be an exciting year for you guys. Just looking at the commercial preparation for deramiocel, what additional color can you tell us about the prep and the division of labor between you and Nippon Shinyaku? And how much of a benefit will it be with their existing commercial infrastructure?

偉大的。非常感謝，並祝賀您取得的所有進展。對你們來說這將是令人興奮的一年。僅從 deramiocel 的商業化準備來看，您能否向我們詳細介紹您和 Nippon Shinyaku 之間的準備工作和分工？這對他們現有的商業基礎設施能帶來多大的好處？

Thanks, Ted. Yeah, great to hear from you as always. So yeah, this has been a really exciting time for Capricor. And obviously, NS is very excited as well. We just keep hitting our milestones as we told them we would.

謝謝，泰德。是的，一如既往地很高興收到您的來信。是的，對於 Capricor 來說，這是一個非常令人興奮的時刻。顯然，NS 也非常興奮。我們只是不斷實現我們承諾的里程碑。

And so they are in full-scale preparation for commercial launch. They have approximately 125 employees in the US that have been dedicated to their Viltepso franchise. So they're well in ensconced in the Duchenne space. They're spending a significant amount of their time now focusing on getting Duchenne ready for commercialization.

他們正在全力準備商業發布。他們在美國擁有約 125 名員工，致力於 Viltepso 特許經營業務。所以它們在杜氏空間中安居得很好。他們現在花了大量的時間致力於杜氏肌肉營養不良症的商業化準備。

What that means in the trenches way is that we are working with them on a day-to-day basis building out modeling for forecasting of market penetration, first year launch activities, working with physicians and also potential infusion centers to make sure that, that's set up and organized market access, meeting with payers now that's in full speed now that we have an accepted BLA. And all of the pieces are in place.

從根本上來說，這意味著我們每天都在與他們合作，建立預測市場滲透率的模型、第一年上市活動，與醫生以及潛在的輸液中心合作，以確保建立和組織市場准入，現在我們已經有了一個公認的 BLA，可以全速與付款人會面。所有部件都已到位。

Our role is primarily to shepherd deramiocel to market. Their role is to sell it and distribute it. And obviously, part of selling a biologic like deramiocel is a deep understanding of the product, which we are providing to them. So we're very, very excited about their energy and also working very closely with them on launch.

我們的職責主要是將 deramiocel 推向市場。他們的職責是銷售和分銷它。顯然，銷售像 deramiocel 這樣的生物製劑的一部分是對我們向他們提供的產品的深入了解。因此，我們對他們的活力感到非常興奮，並且在發布會上與他們密切合作。

Great. Thank you very much.

偉大的。非常感謝。

Yes\ah. Take care, Ted.

是啊。保重，泰德。

Leland Gershell, Oppenheimer.

利蘭·格謝爾，奧本海默。

Hi. Good afternoon. Great to hear all the progress and we're looking forward to events coming later this year for Capricor.

你好。午安.很高興聽到所有的進展，我們期待今年稍後 Capricor 的活動。

Just a few questions from us. First, Linda, I want to ask with respect to your discussions with payers so far. I'm wondering, if as part of those discussions, there was any contemplation of -- for patients who may be on other premium-priced drugs for DMD and then may be also going on deramiocel or even vice versa. Just wondering, given the expense burden of having two premium-priced drugs for this condition, how are the payers viewing that, if you have any intelligence there?

我們只想問幾個問題。首先，琳達，我想問您迄今為止與付款人的討論情況。我想知道，在這些討論中，是否考慮過——對於那些可能正在服用其他高價 DMD 藥物的患者，他們可能也會服用 deramiocel，反之亦然。我只是想知道，考慮到治療這種疾病需要兩種高價藥物的費用負擔，如果您有任何了解的話，付款人是如何看待這一點的？

Yeah. So we've had really good feedback Leland, from the payers so far. There are several reasons why I think this is going to be a great opportunity for reimbursement. Number one, and first and foremost, it is the only therapeutic that will be treating the Duchenne cardiomyopathy. This cannot be highlighted enough.

是的。因此，到目前為止，我們從付款人那裡得到了非常好的回饋。有幾個原因讓我認為這將是一個很好的報銷機會。首先，最重要的是，它是唯一可以治療杜氏心肌病變的療法。這一點無論怎樣強調都不為過。

You were talking about a disease where not only is cardiac disease one of the primary features of the pathophysiology, but also has been indicated to be more and more important as potentially treatments for the dystrophinopathy could become more relevant, such as a gene therapy. We see long-term benefit year over year.

您談論的這種疾病不僅是心臟病是其病理生理學的主要特徵之一，而且已被證明越來越重要，因為肌肉營養不良症的潛在治療方法可能變得更加相關，例如基因療法。我們逐年看到長期利益。

We've seen three years of improvement or stabilization in cardiac as well as skeletal muscle function, which we've shown not only to the FDA, but are also presenting to the payers. So overall, we think that when they have their, sort of, pharmacopeia to pick from in treating Duchenne, this will be a great opportunity to provide, therapeutic benefits to an area that has largely been unaddressed, can reduce hospitalization and mortality, and will go along with any of the other treatments for the dystrophinopathies.

我們已經看到心臟和骨骼肌功能在三年內得到改善或穩定，我們不僅向 FDA 展示了這一點，而且還向付款人展示了這一點。所以總的來說，我們認為，當他們有自己的藥典可供選擇來治療杜氏肌肉營養不良症時，這將是一個很好的機會，為一個很大程度上尚未得到解決的領域提供治療益處，可以減少住院和死亡率，並將與任何其他治療肌肉營養不良症的藥物一起使用。

All right. Thank you. And then a question just longer term, you've got a healthy cash balance. You're going to have the $80 million, presumably on the FDA approval and then that -- and the PRV, which you could monetize, and that doesn't even include other terms with NS, with Japan and potentially Europe.

好的。謝謝。然後問題是，從長期來看，您擁有健康的現金餘額。你將獲得 8000 萬美元，大概是獲得 FDA 批准後獲得的，然後是 PRV，你可以將其貨幣化，這甚至還不包括與 NS、日本以及潛在的歐洲的其他條款。

Just curious, given that the operating expense for Capricor will remain relatively lean given that you wouldn't have to be building your own sales force and getting into commercial infrastructure yourselves. Any thoughts on how you may invest that capital?

只是好奇，考慮到您不必自己建立銷售團隊並進入商業基礎設施，Capricor 的營運費用將保持相對精簡。您對於如何投資這筆資金有什麼想法嗎？

Obviously, exosomes are very promising. But given the stage of that development, it doesn't really seem like it would be expensive to be running those initial studies. Just wondering, if you have any thoughts on where to apply the much greater balance sheet that you may be coming into. Thanks.

顯然，外泌體非常有前景。但考慮到目前的發展階段，進行這些初步研究似乎並不需要花費太多成本。只是想知道，您是否對於將即將出現的更大的資產負債表應用於何處有什麼想法。謝謝。

Yeah. Thank you, Leland. We really appreciate the question. And it's actually been an area of exploration within the company right now. We're looking at all types of opportunities, not only in terms of label expansion for skeletal muscle myopathy of Duchenne, and also Becker, which can further enhance our balance sheet as we move forward.

是的。謝謝你，利蘭。我們非常感謝您的提問。這實際上已經成為公司內部正在探索的一個領域。我們正在尋找各種機會，不僅是杜氏骨骼肌肌病變的標籤擴展，還有貝克爾，這可以進一步增強我們的資產負債表。

Yes, we are focusing on our exosome pipeline. I talked a little bit about that. It is farther behind deramiocel. And we'll be keeping you and the Street updated as we evaluate the opportunities to move this company forward, which we think will be plenty over the next few years.

是的，我們專注於外泌體管道。我稍微談了一下這個。它比 deramiocel 落後得更遠。我們將持續向您和華爾街通報最新情況，評估推動該公司前進的機會，我們認為未來幾年將會有很多機會。

Alright. Thanks for the color.

好吧。謝謝你的顏色。

Thanks, Leland.

謝謝，利蘭。

Joe Pantginis, H.C. Wainwright.

喬·潘吉尼斯（H.C.）溫賴特。

Hey, Linda and AJ. Thanks for taking the questions. So first, maybe for AJ, I mean, this is fantastic news also that Linda, you just announced about the new expanded 25,000-square foot facility. Are you able to define the cost and time frame for this facility?

嘿，琳達和 AJ。感謝您回答這些問題。首先，也許對於 AJ 來說，我的意思是，這也是一個好消息，琳達，你剛剛宣布了新的擴建的 25,000 平方英尺的設施。您能確定該設施的成本和時間範圍嗎？

Yeah. Thanks, Joe. Yeah, we are excited about the expansion. It's in our current footprint here in San Diego, basically the floor above where we're already operating and we're kicking off all the planning right as we speak to expand out. We haven't put out the formal estimates, but I will say we built our original clean room, our commercial qualified clean room here in San Diego for just under a couple of million dollars.

是的。謝謝，喬。是的，我們對擴張感到很興奮。它位於我們目前在聖地亞哥的所在地，基本上是我們已經運營的樓上，我們正​​在啟動所有的擴張計劃。我們還沒有公佈正式的預算，但我要說的是，我們在聖地牙哥建造了最初的無塵室，即商業合格潔淨室，花費了將近幾百萬美元。

So we have the plans in place. We have the team in place. We already have the construction operations underway. So we envision that we can do this to a very reasonable number, and we'll put more of that out there in the coming months as we move ahead.

所以我們已經制定了計劃。我們已經組建了團隊。我們的施工工作已在進行中。因此，我們設想我們可以將這一數字做到非常合理，並且在未來幾個月內，我們將實現更多的目標。

Got it. And then I guess second question is, obviously, you have no indication that there's going to be an ADCOM right now. When do you think you might hear an answer? And for example, if there were an ADCOM, would that be a place that they might want to not necessarily require but maybe force a discussion regarding HOPE-3?

知道了。然後我想第二個問題是，顯然，你現在沒有跡象表明將會有一個 ADCOM。您認為什麼時候可以聽到答案？例如，如果有一個 ADCOM，他們是否可能不一定會要求在那裡進行有關 HOPE-3 的討論？

Yeah. Thanks, Joe. Yeah. So we're waiting every day to hear from them on whether they would want an AdCom. They will need some time to put it together.

是的。謝謝，喬。是的。因此，我們每天都在等待他們的回复，以了解他們是否想要成立 AdCom。他們需要一些時間來將其整合在一起。

And even though we're actively prepping for one as we speak, they have to give us time to prepare as well. So we expect to hear soon. I think part of the delay is just based on some of the turmoil that's going on in the government right now. And so I expect that things are moving at a different pace than they might have even just a few months ago. So stay tuned.

儘管我們正在積極地為此做準備，但他們也必須給我們時間準備。因此我們期待很快得到消息。我認為，部分延遲只是由於政府內部目前出現的一些動盪。因此我預計事情的發展速度可能與幾個月前有所不同。敬請關注。

When we know, we will let everybody else know. We see an AdCom neither as a benefit nor a risk. We believe very strongly in our application. We have clinically and statistically significant data. The data stands on its own.

當我們知道時，我們會告知其他人。我們認為 AdCom 既不是好處也不是風險。我們對我們的應用非常有信心。我們擁有具有臨床和統計學意義的數據。數據本身就是獨立的。

However, if we need to get up there and talk about it, we will absolutely do that. In terms of HOPE-3, what they have told us is that they are not considering HOPE-3 for this biologics license application that they understand that the primary efficacy endpoint of HOPE-3 is skeletal muscle that, that would be used for post-approval label expansion. We plan on taking HOPE-3 potentially outside the US to order to expand our global footprint.

然而，如果我們需要站出來談論這個問題，我們絕對會這樣做。就 HOPE-3 而言，他們告訴我們，他們沒有考慮將 HOPE-3 用於該生物製劑許可申請，​​他們了解 HOPE-3 的主要療效終點是骨骼肌，這將用於上市後標籤擴展。我們計劃將 HOPE-3 帶到美國境外，以擴大我們的全球影響力。

And the focus of this application as we and they understand it is the data that we've talked about, which is the HOPE-2 data, the HOPE-2 open-label extension data compared to the natural history data set from the Cardiac Consortium.

正如我們和他們所理解的，這個應用的重點是我們討論過的數據，即 HOPE-2 數據，HOPE-2 開放標籤擴展數據與心臟聯盟的自然歷史數據集的比較。

And so I don't anticipate a discussion of HOPE-3 at an ADCOM, but if it comes up, we'll be ready to take those questions as well.

因此，我預計 ADCOM 不會討論 HOPE-3，但如果出現討論，我們也準備好回答這些問題。

Also very helpful, thanks for the repetition there. Quickly, just on the discussion about cash usage going forward. Obviously, you talked about some of the obvious things. Since you guys really have a specialty in, say, cellular therapy here, would you consider in-licensing, number one?

也非常有幫助，感謝您的重複。很快，我們就討論一下未來現金的使用情況。顯然，您談論了一些顯而易見的事情。既然你們在細胞療法方面確實有專長，那你們會考慮引進許可嗎？

And then second, with regard to Europe, I know you can't really -- or can't necessarily describe the first part of the question, but what are the outstanding things that you're still needing or the open questions with regard to potential signed NS partnership?

其次，關於歐洲，我知道您無法真正——或者無法描述問題的第一部分，但對於可能簽署的 NS 夥伴關係，您仍然需要解決哪些未完成的事情或懸而未決的問題？

And then also, what are the outstanding questions you feel are important for your EMEA discussions?

此外，您認為對於 EMEA 討論來說哪些未解決的問題很重要？

Yeah. Thanks. So Joe, that's a multi-pronged question. So in terms of in-licensing, we're evaluating opportunities as they become available. Right now, we are laser focusing on getting deramiocel approved and getting that ready to launch.

是的。謝謝。喬，這是一個多方面的問題。因此，就許可而言，我們正在評估可用的機會。目前，我們正專注於獲得 deramiocel 的批准並做好上市準備。

That's going to obviously drive our cash value and our abilities to look at new opportunities. I will say this we are experts now in translational medicine and bringing things from the colloquial bench to now commercial. So we would not rule out the right opportunity should it be presented to us.

這顯然會提高我們的現金價值和尋找新機會的能力。我想說的是，我們現在是轉化醫學領域的專家，可以將醫學成果從口語轉化為商業化。因此，如果有合適的機會呈現在我們面前，我們不會排除。

Having said that, shifting to your second question about the EMA, what we're doing and what we're really focusing on now is the ability to get deramiocel to Europe. We are working right now with EMA and with consultants outside the US in order to build that program. We will be meeting with EMA, hopefully, in the second quarter of this year to further understand what their requirements are for approval of deramiocel.

話雖如此，請轉到您關於 EMA 的第二個問題，我們正在做的事情以及我們現在真正關注的是將 deramiocel 引入歐洲的能力。我們目前正在與 EMA 以及美國以外的顧問合作以建立該計劃。我們希望在今年第二季與 EMA 會面，以進一步了解他們對 deramiocel 批准的要求。

Because we are working directly with Europe right now and because we are seeing some success by getting designations in Europe of ATMP and working with EMA, we are slowing down a little bit our conversations to make sure that we have the best path forward for deramiocel in Europe. We are still negotiating with NS and have an active conversation going in terms of the definitive agreement and really feel very positive about their commitment to the therapeutic.

因為我們目前正在與歐洲直接合作，而且我們透過在歐洲獲得 ATMP 的指定以及與 EMA 的合作取得了一些成功，所以我們正在放慢對話速度，以確保我們在歐洲為 deramiocel 找到最好的發展道路。我們仍在與 NS 進行談判，並就最終協議進行積極對話，對他們對治療的承諾感到非常樂觀。

Really appreciate all the color. Thanks a lot.

真的很欣賞所有的顏色。多謝。

Thanks, Joe. Take good care.

謝謝，喬。好好保重。

Kristen Kluska, Cantor.

克里斯汀·克魯斯卡（Kristen Kluska），領唱。

Hi, everyone. Congrats on the data this week and the recent filing acceptance. So I know that your mechanism is complementary to a gene therapy, but after yesterday's unfortunate news regarding the patient on Elevidys, we are hearing doctors emphasize the need for treatment options for non-ambulatory patients in particular. So can you just remind us what percent of the later-stage population in particular, would have cardiomyopathy? And then while label expansion could come later, could you reference some of your pool data if you have an approval as perhaps supportive evidence? Thank you.

大家好。祝賀本週的數據和最近的申請被接受。所以我知道您的機制是基因療法的補充，但在昨天有關使用 Elevidys 的患者的不幸消息傳來後，我們聽到醫生強調特別需要為無法行走的患者提供治療選擇。那麼，您能否提醒我們，特別是在晚期人群中，有多少比例的人會患有心肌病變？然後，雖然標籤擴充可能會稍後進行，但如果您獲得批准，您是否可以引用一些池資料作為支援證據？謝謝。

Yeah. Thanks, Kristen. Yeah, I think the entire community is reeling from the death of that young man. It's a small patient community. And so -- the loss of one life is tragic always, but especially in a community such as this.

是的。謝謝，克里斯汀。是的，我認為整個社區都因那位年輕人的死亡而悲痛欲絕。這是一個很小的患者社群。所以——失去一條生命總是悲劇，尤其是在這樣的社區。

Most of our patients that we've treated have been non-ambulant. They are primarily the ones that have the cardiomyopathy manifestations, although we've been messaging that the scar that causes the ultimate decline in cardiac function is there when they are little. So we're going to try and get in as young as possible. But yes, most of our patients are the later-stage non-ambulant. The focus of this application is the cardiomyopathy.

我們治療過的大多數患者都無法行走。他們主要是有心肌病變表現的人，儘管我們一直在傳達這樣的訊息：導致最終導致心臟功能衰退的傷疤在他們小時候就已經存在了。因此，我們會嘗試讓孩子盡可能年輕地加入。但是的，我們的大多數患者都是晚期無法行走的患者。本應用的重點是心肌病變。

But as you just correctly stated, we have shown year-over-year improvement in performance in the upper limb in our open-label extension guides. And all of those guys are non-ambulant. So we do believe that deramiocel is -- has been and will continue to be a very good option for those that are at later stages, non-ambulant of the disease and look forward to taking that across the line as well in the future.

但正如您剛才正確指出的那樣，我們在開放標籤擴展指南中顯示了上肢性能的逐年改善。所有這些人都不能行走。因此，我們確實相信，對於處於晚期、無法行走的患者來說，deramiocel 一直是一個非常好的選擇，並且將繼續如此，我們期待在未來也能實現這一目標。

Thank you for that. And then another question. I know you have robust safety data as well. But as we start to think about the potential to move to commercialization where there will be the potential for more to get treatment at once, is there anything we should consider from a safety protocol? Will physicians want to treat a few patients first? Or will doctors require a more extensive testing?

謝謝你。然後是另一個問題。我知道您也擁有可靠的安全資料。但是，當我們開始考慮轉向商業化的可能性時，將有可能讓更多的人同時接受治療，我們是否應該從安全協議中考慮什麼？醫生會願意先治療幾個病人嗎？或者醫生是否需要進行更廣泛的測試？

And the reason why I ask is sometimes like we are seeing with the gene therapy that there's a plethora of different specialists that need to be involved because of some of the known safety risks of that.

我之所以問這個問題，是因為有時就像我們看到的基因療法一樣，由於已知的一些安全風險，需要大量不同的專家參與。

Yeah. Thanks. So I think the Duchenne community, and I've been the beneficiary of participating in many of this symposia have been talking about the care teams necessary for gene therapy for several years. The gene therapies are very complicated because they use viral vectors. And as you know, the immune system doesn't usually like it when a virus enters the system.

是的。謝謝。因此我認為杜氏肌肉營養不良症社群和我作為參加過許多此類研討會的受益者，多年來一直在討論基因療法所需的護理團隊。基因療法非常複雜，因為它們使用病毒載體。眾所周知，免疫系統通常不喜歡病毒進入身體。

And so you have to do a lot of preplanning and pretreatment to mitigate that immune response. In terms of deramiocel, it's a cell therapy. We are not doing any genetic manipulation of it. We've performed over 700 infusions and not seen any serious safety events since the early-stage hypersensitivity, which has been mitigated by pretreatment with antihistamines and steroids. And the abundance of caution, we will do our infusions at infusion centers or in care centers should a hypersensitivity response ever occur.

因此，您必須進行大量的預先計劃和預先處理來減輕免疫反應。就 deramiocel 而言，它是一種細胞療法。我們沒有對其進行任何基因操作。我們已經進行了 700 多次輸液，自早期超敏反應以來沒有發現任何嚴重的安全事件，透過使用抗組織胺和類固醇進行預處理可以緩解這種症狀。為了謹慎起見，如果發生過敏反應，我們將在輸液中心或護理中心進行輸液。

We don't anticipating needing a care team. It's a very simple infusion and the side effects, which are mild and a little bit of mild flu-like symptoms in some of our patients are easily mitigated and understood by our investigators. So I don't think it's going to have the same complicated introduction or care paradigm needed as a gene therapy.

我們預計不需要護理團隊。這是一種非常簡單的輸液，副作用很輕微，我們的一些患者可能會出現輕微的流感樣症狀，我們的研究人員可以輕鬆緩解和理解。因此我認為它不需要像基因療法那樣複雜的引入或護理模式。

Thanks. And last question for me. I think you commented that with the additional manufacturing footprint, this could support 2,000 to 3,000 patients potentially as early as mid-2026. But should you get an approval later this year, how should we be thinking about what you can essentially handle until that time? Because I know you said there's already some patients that want to transfer on OLE as well as others that weren't involved in the trial that are aware of the potential of the drug. Thanks, again, everyone.

謝謝。這是我的最後一個問題。我認為您曾評論說，隨著製造足跡的增加，最早可以在 2026 年中期為 2,000 至 3,000 名患者提供支持。但是如果您在今年稍後獲得批准，我們應該如何考慮您在此之前能夠處理哪些事情？因為我知道您說過，已經有一些患者想要轉用 OLE，還有一些未參與試驗的患者也意識到了該藥物的潛力。再次感謝大家。

No, thanks, Kristen. Yeah. So our manufacturing facility here in San Diego, which we built in anticipation of commercial launch can service between 250, 500 patients per year. If you actually look at the time line of launch, we're looking all things considered at a Q4 launch this year.

不，謝謝，克里斯汀。是的。因此，我們位於聖地牙哥的製造工廠是為了商業化而建造的，每年可以為 250,500 名患者提供服務。如果你真的看一下發布的時間表，我們會考慮在今年第四季發布的所有事項。

By the time the new facility comes on, it won't even be a full year into commercialization. And so we believe that we'll have enough from our small-scale commercial facility in San Diego to meet early demand and then be able to swing right away into the new facility.

等到新工廠投入使用時，距離商業化不到一年。因此，我們相信，我們位於聖地牙哥的小型商業設施將有足夠的產能來滿足早期需求，然後能夠立即轉入新設施。

As we mentioned, but I'll highlight, the new facility is actually within the footprint of our currently existing manufacturing plant. And so we're hopeful that the regulatory obligations required to bring that facility online will be light, and therefore, we'll be able to get it on board as soon as possible after launch.

正如我們所提到的，但我要強調的是，新工廠實際上位於我們現有製造工廠的佔地面積內。因此，我們希望該設施上線所需的監管義務會比較輕鬆，這樣我們就能在啟動後儘快將其投入使用。

Thank you so much, again.

再次感謝您。

Thanks.

謝謝。

Catherine Novack, Jones Trading.

凱瑟琳·諾瓦克，瓊斯貿易公司。

Hi. Good afternoon, everyone. Thanks for taking my question. I'm just wondering if you can talk a little bit about -- in the past, FDA had made comments about the issues of single-arm studies in DMD due to the disease heterogeneity. Can you just give us some color about in your discussions with FDA, what have they brought up regarding their view on cardiac outcomes shown in HOPE-2 OLE, why this might be -- why they might take a different approach on this?

你好。大家下午好。感謝您回答我的問題。我只是想知道您是否可以稍微談談——過去，FDA 曾對由於疾病異質性而導致的 DMD 單臂研究問題發表過評論。您能否向我們介紹一下您與 FDA 的討論，他們對 HOPE-2 OLE 中顯示的心臟結果有何看法，為什麼會這樣——為什麼他們可能會對此採取不同的方法？

Thanks. So I think what you're asking is because the HOPE-2 open-label extension study is not placebo-controlled, how is FDA looking at that data? Am I understanding that correctly?

謝謝。所以我認為您要問的是，由於 HOPE-2 開放標籤擴展研究不是安慰劑對照的，FDA 如何看待這些數據？我的理解正確嗎？

Correct.

正確的。

Okay. Yeah. So there's a couple of very important points there, and thanks so much for calling in. Number one is, we have had access to propensity matched age function medication matched set of patients from the Vanderbilt natural history, cardiac consortium study funded by the FDA to be able to use as an indicator of what would be considered a placebo group, right, a group that has been untreated. And we can, therefore, look at the natural history of the cardiomyopathy compared to the open-label extension guys in a year-over-year manner.

好的。是的。這裡有幾個非常重要的觀點，非常感謝您的來電。首先，我們獲得了范德比爾特自然史、心臟聯盟研究（由 FDA 資助）的傾向匹配年齡功能藥物匹配患者組，以便能夠將其作為安慰劑組（即未接受治療的組）的指標。因此，我們可以與開放標籤擴展研究者進行逐年對比，觀察心肌病變的自然病程。

Typically, this would be an issue if you were doing a type of volitional measurement like a North Star Ambulatory assessment of time to rise or in our case, the performance of the upper limb because one might say, well, if you know you're getting treated, you're going to maybe function or perform better.

通常，如果您正在進行某種意志測量，例如北極星門診評估起床時間，或者在我們的案例中評估上肢的表現，那麼這將是一個問題，因為有人可能會說，如果您知道自己正在接受治療，那麼您的功能或表現可能會更好。

The beauty of this data set and the reason the FDA has been willing to look at it so carefully is because nothing about cardiac MRI is volitional. You cannot wish your heart better. You cannot wake up and think I'm going to get a cellular therapy and therefore, my heart is going to function better. So even though the data set is relatively small, it's very concise in its ability to measure function.

這個資料集的美妙之處以及 FDA 願意如此仔細研究它的原因在於心臟 MRI 沒有任何主觀因素。你無法希望自己的心變得更好。你不能一醒來就想著我要接受細胞療法，這樣我的心臟就會功能更好。因此，儘管資料集相對較小，但其測量功能的能力卻非常簡潔。

Our strong statistical significance is emblematic of the strong treatment effect that we are seeing. That means that very little opportunity for this data to be up to chance. And so as a result of that, we remain confident that this is not a typical single-arm study, but one that actually has a natural history real-world evidence component that supports the data.

我們強大的統計意義象徵著我們所看到的強大的治療效果。這意味著這些數據受到偶然因素影響的可能性很小。因此，我們仍然相信這不是一項典型的單臂研究，而是一項實際上具有支持數據的自然史真實世界證據成分的研究。

Got it. Thanks. Thanks so much.

知道了。謝謝。非常感謝。

Thank you.

謝謝。

Aydin Huseynov, Ladenburg.

拉登堡的艾登‧胡賽諾夫 (Aydin Huseynov)。

Hi. Good afternoon, everyone. Congratulations for the progress this quarter. So a couple of questions from us. So Linda, I think you mentioned heart diseases where deramiocel might be helpful. And obviously, the next indication, the next low-hanging fruit is Becker Muscular Dystrophy. It's in your corporate presentation.

你好。大家下午好。恭喜本季取得的進展。我們有幾個問題。所以琳達，我認為你提到了德拉米奧塞爾可能對心臟病有幫助。顯然，下一個跡象、下一個唾手可得的成果就是貝克爾肌肉營養不良症。它在您的公司介紹中。

So when do you think we will have updates on the potential Becker Muscular Dystrophy trial design and whether it is going to look like HOPE-2? So could you give us a little bit of insights in terms of what is your clinical strategy as it comes to Becker Muscular Dystrophy?

那麼您認為我們什麼時候可以獲得有關貝克爾肌肉營養不良症潛在試驗設計的最新消息，以及它是否會像 HOPE-2 一樣？那麼，您能否就貝克爾肌肉營養不良症的臨床策略向我們提供一些見解？

Thanks, Aydin. Yeah, it's funny as I was putting together my remarks today, I was thinking a little bit about you, and I knew that you'd come to me with the Becker question. So we're working with the agency now on some of the initial steps of getting our program going with Becker. We've submitted some requests to them recently. Our focus is to get deramiocel approved for Duchenne and then begin our emphasis on building towards Becker for which, by the way, we hold all the economics.

謝謝，艾登。是的，有趣的是，當我今天整理我的演講時，我有點想到了你，而且我知道你會向我提出貝克爾的問題。因此，我們現在正與該機構合作，採取一些初步措施，使我們的計畫與貝克爾一起順利實施。我們最近向他們提交了一些請求。我們的重點是讓德拉米奧塞爾 (deramiocel) 獲得杜氏肌肉營養不良症 (Duchenne) 的批准，然後開始致力於開發貝克爾 (Becker) 療法，順便說一句，我們掌握著貝克爾療法的所有經濟效益。

NS has no rights to those. Our goal will be to convince the agency that the cardiomyopathy associated with Becker looks and functionally is the same as the Duchenne cardiomyopathy and see if we can potentially move towards an accelerated pathway in Becker. We are bringing in key opinion leaders literally as we speak and medical expertise to Capricor to help us build out our Becker program, and I expect to have more color for that program over the next quarter or two.

NS 對此沒有權利。我們的目標是讓該機構相信，貝克爾病相關的心肌病變在外觀和功能上與杜氏心肌病變相同，並看看我們是否有可能在貝克爾病中加速治療。我們正在為 Capricor 引入關鍵意見領袖和醫學專業知識，以幫助我們建立 Becker 計劃，我預計該計劃將在未來一兩個季度內呈現更多亮點。

Okay. Understood. Thank you. Thank you for the update. And what are other heart diseases where you think deramiocel can make a meaningful difference? I'm just trying to understand the whole commercial potential for deramiocel beyond DMD and beyond BMD.

好的。明白了。謝謝。感謝您的更新。您認為 deramiocel 還能對哪些其他心臟病疾病產生重大影響？我只是想了解 deramiocel 除了 DMD 和 BMD 之外的整個商業潛力。

Well, look, this is an area of great interest to Capricor right now. We have a very powerful therapeutic, a defined mechanism of action, which is immunomodulatory that drives antifibrotic activity. We're evaluating orphan cardiomyopathies, looking at where we might best deploy them.

嗯，看，這是 Capricor 目前非常感興趣的領域。我們擁有一種非常強大的治療方法，其作用機制明確，具有免疫調節作用，可驅動抗纖維化活性。我們正在評估孤兒心肌病變，尋找最佳的治療方法。

I think many of the physicians in the colloquial room, including yourself, have ideas of where that could be. And we'll provide some updates on pipeline expansion into other orphan cardiomyopathies as we begin to evaluate them and determine that, that would be the best path forward for deramiocel.

我認為討論室裡的許多醫生，包括您自己，都知道這可能在哪裡。當我們開始評估其他罕見心肌病變的治療方案並確定這是 deramiocel 的最佳發展方向時，我們將提供一些關於該藥物在治療其他罕見心肌病變方面的管道擴展的最新資訊。

Okay. Thank you. Thanks so much.

好的。謝謝。非常感謝。

Yeah. Thank you. Have a great day.

是的。謝謝。祝你有美好的一天。

Madison El-Saadi, B. Riley Securities.

麥迪遜·埃爾薩迪 (Madison El-Saadi)，B. Riley 證券。

Hey, Linda and AJ. Thank you for taking our question and congrats on the progress. I'm coming away from MDA, so my question may be a bit academic, so forgive me. So based on what you've seen through the course of deramiocel's development, what do you think is the ideal baseline ejection fraction baseline where impact will be the highest? Is it in the, for example, less than 35% range? Or is it more the 35% to 45% range?

嘿，琳達和 AJ。感謝您回答我們的問題，並祝賀取得的進展。我剛離開 MDA，所以我的問題可能有點學術性，請原諒我。那麼，根據您在 deramiocel 開發過程中所看到的情況，您認為理想的基線射血分數基線是多少，其影響會達到最高？例如，它是否在低於 35% 的範圍內？還是更接近 35% 到 45% 的範圍？

And then secondly, I believe you mentioned that you would expect 7,500 boys to be eligible. Would this be based on a hard ejection fraction threshold? And I ask given that cardiac treatment in this population is often the result of shared decision-making. Thanks.

其次，我相信您提到過，預計有 7,500 名男孩符合資格。這會基於硬射血分數閾值嗎？我之所以會提出這個問題，是因為該族群的心臟病治療往往是共同決策的結果。謝謝。

Yeah, Madison. Thank you so much and I hope you enjoyed the MDA. So what we understand about the cutoff for ejection fraction is that, if we can get in there early, we believe that we will see the greatest long-term benefit in terms of stabilization of disease progression.

是的，麥迪遜。非常感謝您，希望您喜歡 MDA。因此，我們對射血分數截止值的理解是，如果我們能夠儘早到達那裡，我們相信我們將在穩定疾病進展方面看到最大的長期益處。

So in the patients with ejection fractions of 45% or greater, we see the greatest amount of long-term stabilization and some of our patients haven't seen any decline in ejection fraction literally in years. And that is because we believe that once you have the immunomodulation, antifibrotic, you're actually preserving the healthy heart tissue that does exist. Having said that, we have patients that have had lower ejection fractions where we're also seeing stabilization of the disease process.

因此，對於射血分數為 45% 或更高的患者，我們看到了最大程度的長期穩定性，並且我們的一些患者多年來沒有出現射血分數的任何下降。這是因為我們相信，一旦有了免疫調節和抗纖維化，你實際上就保留了現有的健康心臟組織。話雖如此，我們也看到射血分數較低的患者的病情進展趨於穩定。

What I can say overall is that, early treatment is better because you have a longer opportunity with -- or a better opportunity, not say longer, but a better opportunity to treat the disease process early, preserve cardiac function and also obviously then hopefully sustain life and not only quantity but quality of life. So we're still open to all comers in terms of ejection fractions. We do know that once they get below a certain point, once they get to what would be considered an end-stage heart failure, it's harder and harder to bring them back from that edge.

總的來說，我可以說，早期治療更好，因為你有更長的機會——或者更好的機會，不是說更長，而是有更好的機會來儘早治療疾病過程，保護心臟功能，並且顯然希望維持生命，不僅是生命的數量，還有生命質量。因此，就射血分數而言，我們仍然對所有參與者持開放態度。我們確實知道，一旦他們的病情低於某個點，一旦他們進入被認為是終末期心臟衰竭的階段，就越來越難以將他們從這種邊緣狀態中拯救出來。

And so that's what we're messaging to the agency as well as to physician leaders that we need to get in there early. And yes, it will be a decision of the care providers -- we're working now very actively with the cardiologists that treat Duchenne patients, both pediatric and adult as well as the neurologists, so that they become educated and open to the idea of using deramiocel as part of the treatment paradigm for DMD cardiomyopathy.

這就是我們向機構以及醫生領導者傳達的訊息：我們需要儘早介入。是的，這將是護理提供者的決定——我們現在正積極地與治療杜氏肌肉營養不良症患者的心臟病專家（包括兒童和成人）以及神經科醫生合作，以便他們了解並接受使用德米奧塞爾作為杜氏肌肉營養不良症心肌病治療範例的一部分的想法。

Understood. Thanks.

明白了。謝謝。

Thank you for your question.

感謝您的提問。

Thank you. I will now turn the call back to Capricor management for final thoughts.

謝謝。現在我將把電話轉回給 Capricor 管理層，徵求他們的最終意見。

Yeah. Thank you for joining today's call. We look forward to updating you on our continued progress over the coming months, and I hope you have a nice evening.

是的。感謝您參加今天的電話會議。我們期待在未來幾個月向您通報我們的持續進展，並祝您度過一個愉快的夜晚。

Thank you, and this concludes today's call. Thank you for participating and you may all disconnect.

謝謝，今天的電話會議到此結束。感謝您的參與，現在您可以斷開連接了。